1. Field of the Invention
The present invention relates to a method for producing optically active 3-substituted-2-norbornanones which are useful as starting materials for several kinds of physiologically active materials, and to the intermediates, optically active 2-hydroxy-2-norbornanecarboxylic acid and to a method for producing these intermediates. As an example, a thromboxane A.sub.2 receptor antagonist useful as an anticoagulant can be synthesized from the above norbornanone. (Narisada et al., J. Med. Chem., 31, 1847(1988), Hamanaka et al., Tetrahedron Lett., 30, 2399(1989)).
2. Description of the Prior Art
Recently the synthesis of physiologically active materials as optically active compounds has become important. When a material has optical isomers, the activities are generally different among isomers. However, only one isomer usually shows strong activities and the other isomers show weak activities or undesired toxicity in many cases. Accordingly, when the plysiologically active materials are especially synthesized for medical supplies, it is required that desired optical isomers are selectively synthesized in order to develop sufficient physiological activities in safety.
To efficiently synthesize optically active 3-substituted-2-norbornanones of the present invention, it is necessary to efficiently obtain optically active 2-norbornanones. As for the synthesis of optically active 2-norbonanones, (1) a optical resolution method of racemic endo- or exo-2-norbornanol by using a diastereomer process (Winstein et al., J. Am. Chem. Soc., 74, 1147(1952), Berson et al., ibid., 83 3986(1961).), (2) a method of asymmetric oxidation or asymmetric reduction of racemic exo-2-norbornanol or 2-norbornanone with a horse liver alcohol dehydrogenase (Irwin et al., J. Am. Chem. Soc., 98, 8476(1976) and the like are reported. However, the method (1) is not efficient because recrystallization of the product should be repeated to improve the optical purity. The method (2) is not practical because a reagent to be used is expensive and the asymmetric yield of the product is low.
As described above, all of these cases are not satisfactory to practice on an industrial level.
For the above reasons, development of a simple process for producing optically active 3-substituted-2-norbornanone widely useful as synthetic intermediates of physiologically active materials has been long-desired.